Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide, with high morbidity and mortality rates. The evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) that modulate cancer cell proliferation, invasion, metastasis, and tumor immunity, including in CRC, has been attracting attention. The present study examined the expression status of CD70 and POSTN in CRC and analyzed their association with clinicopathological features and clinical outcomes. In the present study, in total 15% (40/269) and 44% (119/269) of cases exhibited CD70 and POSTN expression on CAFs, respectively. Co-expression of CD70 and POSTN was detected in 8% (21/269) of patients. Fluorescent immunohistochemistry identified the co-expression of CD70 and POSTN with FAP and PDPN, respectively. ACTA2 was not co-expressed with CD70 or POSTN in CRC CAFs. CRC with CD70+/POSTN+ status in CAFs was significantly associated with distant organ metastasis (p = 0.0020) or incomplete resection status (p = 0.0011). CD70+/POSTN+ status tended to associate with advanced pT stage (p = 0.032) or peritoneal metastasis (p = 0.0059). Multivariate Cox hazards regression analysis identified CD70+/POSTN+ status in CAFs [hazard ratio (HR) = 3.78] as a potential independent risk factor. In vitro experiments revealed the activated phenotypes of colonic fibroblasts induced by CD70 and POSTN, while migration and invasion assays identified enhanced migration and invasion of CRC cells co-cultured with CD70- and POSTN-expressing colonic fibroblasts. On the basis of our observations, CD70 and POSTN immunohistochemistry can be used in the prognostication of CRC patients. CRC CAFs may be a promising target in the treatment of CRC patients.

Characterization of pleural mesothelioma by hierarchical clustering analyses using immune cells within tumor microenvironment.

INTRODUCTION: Over the past decade, classifications using immune cell infiltration have been applied to many types of tumors; however, mesotheliomas have been less frequently evaluated. METHODS: In this study, 60 well-characterized pleural mesotheliomas (PMs) were evaluated immunohistochemically for the characteristics of immune cells within tumor microenvironment (TME) using 10 immunohistochemical markers CD3, CD4, CD8, CD56, CD68, CD163, FOXP3, CD27, PD-1 and TIM-3. For further characterization of PMs, hierarchical clustering analyses using these 10 markers were performed. RESULTS: Among the immune cell markers, CD3 (P < 0.0001), CD4 (P = 0.0016), CD8 (P = 0.00094), CD163+ (P = 0.042) and FOXP3+ (P = 0.025) were significantly associated with unfavorable clinical outcome. Immune checkpoint receptor expressions on tumor-infiltrating lymphocytes such as PD-1 (P = 0.050), CD27 (P = 0.014) and TIM-3 (P = 0.0098) were also associated with unfavorable survival. Hierarchical clustering analyses identified three groups showing specific characteristics and significant associations with patient survival (P = 0.011): the highest number of immune cells (ICHigh); the lowest number of immune cells, especially CD8+ and CD163+ cells (ICLow); and intermediate number of immune cells (ICInt). ICHigh tumors showed significantly higher expression of PD-L1 (P = 0.00038). Cox proportional hazard model identified ICHigh [hazard ratio (HR) = 2.90] and ICInt (HR = 2.97) as potential risk factors compared with ICLow. Tumor CD47 (HR = 2.36), tumor CD70 (HR = 3.04) and tumor PD-L1 (HR = 3.21) expressions were also identified as potential risk factors for PM patients. CONCLUSION: Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.

Rapid evaluation of PHD2 inhibitory activity of natural products based on capillary electrophoresis online stacking strategy.

Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 µM and 5.0 µM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases.

UBD participates in neutrophilic asthma by promoting the activation of IL-17 signaling.

Neutrophilic asthma is a persistent and severe inflammatory lung disease characterized by neutrophil activation and the mechanisms of which are not completely elucidated. Ubiquitin D (UBD) is a ubiquitin-like modifier participating in infections, immune responses, and tumorigenesis, while whether UBD involves in neutrophilic asthma needs further study. In this study, we initially found that UBD expression was significantly elevated and interleukin 17 (IL-17) signaling was enriched in the endobronchial biopsies of severe asthma along with neutrophils increasing by bioinformatics analysis. We further confirmed that UBD was upregulated in the lung tissues of neutrophilic asthma mouse model. UBD overexpression promoted IL-17 signaling activation. Knockdown of UBD suppressed the activation of IL-17 signaling. UBD interacted with TRAF2 and reduced the total and the K48-linked ubiquitination of TRAF2. However, IL-17 A stimulation increased both the total and the K48-linked ubiquitination of TRAF2. Together, these findings indicated that UBD was upregulated and played a critical role in IL-17 signaling which contributed to a better understanding of the complex mechanisms in neutrophilic asthma.

Characterization of colorectal cancer by hierarchical clustering analyses of five immune cell markers.

The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4Low , CD4High , MΦHigh , and CD8Low . MΦHigh tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1-PD-1 and/or CD47-SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.

Ferritinophagy-mediated ferroptosis facilitates methotrexate-induced hepatotoxicity by high-mobility group box 1 (HMGB1).

BACKGROUND AND AIM: Hepatotoxicity is a well-defined reaction to methotrexate (MTX), a drug commonly used for the treatment of rheumatoid arthritis and various tumours. We sought to elucidate the mechanism underlying MTX-induced hepatotoxicity and establish a potentially effective intervention strategy. METHODS: We administered MTX to liver cells and mice and assessed hepatotoxicity by cell viability assay and hepatic pathological changes. We determined ferroptosis and ferritinophagy by detecting ferroptosis-related markers and autophagic degradation of ferritin heavy chain 1 (FTH1). RESULTS: We have shown that hepatocytes treated with MTX undergo ferroptosis, and this process can be attenuated by ferroptosis inhibitors. Interestingly, NCOA4-mediated ferritinophagy was found to be involved in MTX-induced ferroptosis, which was demonstrated by the relief of ferroptosis through the inhibition of autophagy or knockdown of Ncoa4. Furthermore, MTX treatment resulted in the elevation of high-mobility group box 1 (HMGB1) expression. The depletion of Hmgb1 in hepatocytes considerably alleviated MTX-induced hepatotoxicity by limiting autophagy and the subsequent autophagy-dependent ferroptosis. It is noteworthy that glycyrrhizic acid (GA), a precise inhibitor of HMGB1, effectively suppressed autophagy, ferroptosis and hepatotoxicity caused by MTX. CONCLUSION: Our study shows the significant roles of autophagy-dependent ferroptosis and HMGB1 in MTX-induced hepatotoxicity. It emphasizes that the inhibition of ferritinophagy and HMGB1 may have potential as a therapeutic approach for preventing and treating MTX-induced liver injury.

An Analytical Thermal Buckling Model for Semiconductor Chips on a Substrate.

Semiconductor chips on a substrate have a wide range of applications in electronic devices. However, environmental temperature changes may cause mechanical buckling of the chips, resulting in an urgent demand to develop analytical models to study this issue with high efficiency and accuracy such that safety designs can be sought. In this paper, the thermal buckling of chips on a substrate is considered as that of plates on a Winkler elastic foundation and is studied by the symplectic superposition method (SSM) within the symplectic space-based Hamiltonian system. The solution procedure starts by converting the original problem into two subproblems, which are solved by using the separation of variables and the symplectic eigenvector expansion. Through the equivalence between the original problem and the superposition of subproblems, the final analytical thermal buckling solutions are obtained. The SSM does not require any assumptions of solution forms, which is a distinctive advantage compared with traditional analytical methods. Comprehensive numerical results by the SSM for both buckling temperatures and mode shapes are presented and are well validated through comparison with those using the finite element method. With the solutions obtained, the effects of the moduli of elastic foundations and geometric parameters on critical buckling temperatures and buckling mode shapes are investigated.

Gypenoside-14 Reduces Depression via Downregulation of the Nuclear Factor Kappa B (NF-kB) Signaling Pathway on the Lipopolysaccharide (LPS)-Induced Depression Model.

Neuroinflammation is a common pathogenetic sign of depression and is closely linked to the development of depression. Many clinical anti-inflammatory drugs act as antidepressants by reducing the neuroinflammatory response. Previous research found that gypenosides and their bioactive compound gypenoside-14 (GP-14) had neuroprotective effects against hypoxia-induced injury and reduced neuroinflammation-related high-altitude cerebral edema. Here we investigated the effects of GP-14 on the lipopolysaccharide (LPS)-induced depression-like behavior model. LPS (0.5 mg/kg) was injected into mice intraperitoneally for 7 consecutive days to induce depression-like behavior, which is considered a model for the exacerbation of depression. GP-14 in the amount of 100 mg/kg was simultaneously administered by gavage for 7 days. In the LPS-induced depression model, GP-14 not only attenuated depression-like behavior but also improved the anxiety-like behavior of the mice. Additionally, GP-14 treatment mitigated learning and cognitive decline in depressed mice. ELISA and immunofluorescence staining results revealed that GP-14 inhibited the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and suppressed the activation of astrocytes induced with LPS, indicating its potent anti-inflammatory effect. GP-14 pretreatment in C8 cells and primary astrocytes can inhibit the activation of the NF-κB signaling pathway and downregulate the levels of pro-inflammatory factors. In summary, our findings showed that GP-14 had significant anti-inflammation and anti-depression properties; thus, GP-14 could be a promising lead compound for treating depression.

Synaptic transistor with multiple biological functions based on metal-organic frameworks combined with the LIF model of a spiking neural network to recognize temporal information.

Spiking neural networks (SNNs) have immense potential due to their utilization of synaptic plasticity and ability to take advantage of temporal correlation and low power consumption. The leaky integration and firing (LIF) model and spike-timing-dependent plasticity (STDP) are the fundamental components of SNNs. Here, a neural device is first demonstrated by zeolitic imidazolate frameworks (ZIFs) as an essential part of the synaptic transistor to simulate SNNs. Significantly, three kinds of typical functions between neurons, the memory function achieved through the hippocampus, synaptic weight regulation and membrane potential triggered by ion migration, are effectively described through short-term memory/long-term memory (STM/LTM), long-term depression/long-term potentiation (LTD/LTP) and LIF, respectively. Furthermore, the update rule of iteration weight in the backpropagation based on the time interval between presynaptic and postsynaptic pulses is extracted and fitted from the STDP. In addition, the postsynaptic currents of the channel directly connect to the very large scale integration (VLSI) implementation of the LIF mode that can convert high-frequency information into spare pulses based on the threshold of membrane potential. The leaky integrator block, firing/detector block and frequency adaptation block instantaneously release the accumulated voltage to form pulses. Finally, we recode the steady-state visual evoked potentials (SSVEPs) belonging to the electroencephalogram (EEG) with filter characteristics of LIF. SNNs deeply fused by synaptic transistors are designed to recognize the 40 different frequencies of EEG and improve accuracy to 95.1%. This work represents an advanced contribution to brain-like chips and promotes the systematization and diversification of artificial intelligence.

Review of oxygen-enhanced lung mri: Pulse sequences for image acquisition and T1 measurement.

Oxygen-enhanced MR imaging (OE-MRI) is a special proton imaging technique that can be performed without modifying the scanner hardware. Many fundamental studies have been conducted following the initial reporting of this technique in 1996, illustrating the high potential for its clinical application. This review aims to summarise and analyse current pulse sequences and T1 measurement methods for OE-MRI, including fundamental theories, existing pulse sequences applied to OE-MRI acquisition and T1 mapping. Wash-in and wash-out time identify lung function and are sensitive to ventilation; thus, dynamic OE-MRI is also discussed in this review. We compare OE-MRI with the primary competitive technique, hyperpolarised gas MRI. Finally, an overview of lower-field applications of OE-MRI is highlighted, as relatively recent publications demonstrated positive results. Lower-field OE-MRI, which is lower than 1.5 T, could be an alternative modality for detecting lung diseases. This educational review is aimed at researchers who want a quick summary of the steps needed to perform pulmonary OE-MRI with a particular focus on sequence design, settings, and quantification methods.

Alkylamides from Zanthoxylum armatum DC. and their neuroprotective activity.

Zanthoxylum armatum DC. is an important medicinal plant, and its pericarps are commonly used as a natural spice in Asian countries. In this study, fifteen alkylamides were isolated and elucidated from the pericarps of Z. armatum, including five undescribed alkylamides (1-5) and ten known compounds (6-15). The molecular structures of all compounds were elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, among which the absolute configuration of compound 15 was determined by the Mo2(OAc)4-induced circular dichroism method. Moreover, all compounds were screened for their neuroprotective activity against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells for the evaluation of their neuroprotective activity. Especially, compounds 2-4 expressed potential neuroprotective activity, and further research showed that the cell viability was significantly enhanced in a concentration dependent manner when the cells were treated for 6 h. Moreover, compounds 2-4 could decrease reactive oxygen species accumulation. This paper enriched structure types of alkylamides in Zanthoxylum armatum.

Experimental Study on Acoustic Emission Characteristics of Uniaxial Compression of MICP-Filled Sandstone.

Rock masses are inherently heterogeneous, with numerous fractures that significantly affect their mechanical properties, fracture characteristics, and acoustic emission features due to the interactions between fractures or between fractures and the rock mass. Microbially induced calcite precipitation (MICP) technology, as an emerging non-destructive biological grouting reinforcement method, can repair fractured rock masses and alter their internal conditions. To investigate the mechanical properties, failure process evolution, and MICP repair effects of sandstone before and after repair, uniaxial compression tests were conducted on prefabricated, fractured (0.7-2.0 mm width) filled and unfilled rock samples, with acoustic emission monitoring throughout the process. Acoustic emission signal characteristics of the rock samples under stress were comparatively analyzed, determining the rock failure process and the microscopic failure types at compression-density stages, elastic stages, and destruction stages. The results show that the properties of the filled specimens improved, the failure process was mitigated, and the final failure stage was dominated by tension signals, accounting for over 60% of the total. The filling effect was better than 1.5-2.0 mm when the fracture width was 0.7-1.0 mm. The study deeply reveals the evolutionary process of compressive failure of the two types of rocks under different fracture widths, and by correlating the acoustic emission parameters with the stress-strain process, it provides a theoretical basis for repairing rock fractures using microbial engineering technology and offers experimental evidence and possible directions for the improvement and optimization of MICP technology.

Study on Multifield Migration and Evolution Law of the Oxidation Heating Process of Coal Spontaneous Combustion in Dynamic Goaf.

To study the dynamic evolution law of the oxidation heating process of coal spontaneous combustion in the goaf during the advancing process of the working face, a dynamic model of oxidation heating of coal spontaneous combustion in the goaf was established on the basis of deformed geometry. Through numerical simulation research, the evolution and migration laws of seepage field, oxygen concentration field, temperature field, and high-temperature area of coal spontaneous combustion in the goaf during the advancement of the working face was obtained. The results indicate that the distribution of the bulking coefficient, porosity, and permeability of the falling coal and rock mass in the goaf is nonuniform. They are relatively large in the area near the working face and the inlet and return airway and remain relatively unchanged with the advancement of the working face, but they are constantly decreasing in the location of the gob in the middle and deep. The oxygen concentration in the goaf presents an asymmetrical distribution. The oxygen concentration distribution area on the inlet side is wider than that on the return air side. At the same depth of the goaf, the oxygen concentration gradually decreases from the inlet side to the return air side; after the advancement distance exceeds 200 m, the air leakage in the goaf basically disappears, and the oxygen concentration decreases to zero. The high-temperature area of coal spontaneous combustion oxidation in the goaf was mainly concentrated on the air inlet side and extended toward the return air side. The advancing speed has a significant effect on the oxidation heating process of coal spontaneous combustion in the dynamic goaf. Under the same propulsion distance, when the advancing speed is 6 m/day, the highest temperature in the goaf is about 40 °C, and when the advancing speed is 2 m/day, the highest temperature in the goaf is as high as 120 °C. The smaller the advancing speed, the higher the heating rate of the goaf and the closer the high-temperature area to the working surface. The higher the advancing speed, the lower the temperature of the high-temperature point of the goaf and the greater the depth of the high-temperature point of the high temperature area; when the advancing speed is 2 m/day, the highest temperature point in the goaf is 70 m away from the working face, whereas when the advancing speed is 6 m/day, it reaches 174.6 m.

Stromal POSTN Enhances Motility of Both Cancer and Stromal Cells and Predicts Poor Survival in Colorectal Cancer.

Evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) has rapidly been accumulating. To uncover clinicopathological importance of periostin (POSTN) expression in colorectal cancer (CRC), the present study immunohistochemically examined its expression status. Furthermore, to reveal its mechanisms involved, molecular experiments were performed. In CRC tissues, 44% of the cases (119/269) exhibited POSTN expression in the CAFs. In contrast, CRC cells expressed POSTN at almost undetectable levels. Survival analyses identified that patients with POSTN-positive CRC had a significantly worse 5-year survival rate (63.2% vs. 81.2%; p = 0.011). Univariate analyses revealed that POSTN positivity was associated with peritoneal (p = 0.0031) and distant organ metastasis (p < 0.001). Furthermore, immunohistochemical analyses identified a significant association between POSTN and p53 complete loss status in CRC cells. Decorin and fibroblast activation protein expression in CAFs was also associated with POSTN. POSTN significantly enhanced the migration of both CRC cells and fibroblasts with FAK and AKT or STAT3 activation, and co-culture assays demonstrated the communication between CRC cells and fibroblasts, which enhanced STAT3 activation in fibroblasts. On the basis of our results, we speculated that stromal POSTN accelerated metastasis via stromal remodeling capacity and activated the migration of both tumor and stromal cells.

Research on Pedestrian Detection Model and Compression Technology for UAV Images.

The large view angle and complex background of UAV images bring many difficulties to the detection of small pedestrian targets in images, which are easy to be detected incorrectly or missed. In addition, the object detection models based on deep learning are usually complex and the high computational resource consumption limits the application scenarios. For small pedestrian detection in UAV images, this paper proposes an improved YOLOv5 method to improve the detection ability of pedestrians by introducing a new small object feature detection layer in the feature fusion layer, and experiments show that the improved method can improve the average precision by 4.4%, which effectively improves the pedestrian detection effect. To address the problem of high computational resource consumption, the model is compressed using channel pruning technology to reduce the consumption of video memory and computing power in the inference process. Experiments show that the model can be compressed to 11.2 MB and the GFLOPs of the model are reduced by 11.9% compared with that before compression under the condition of constant inference accuracy, which is significant for the deployment and application of the model.

Potential Anti-Tumor Activity of Nardoguaianone L Isolated from Nardostachys jatamansi DC. in SW1990 Cells.

Natural products (NPs) were a rich source of diverse bioactive molecules. Most anti-tumor agents were built on natural scaffolds. Nardostachys jatamansi DC. was an important plant used to process the traditional Chinese herbal medicines "gansong". Pancreatic cancer was the fourth most common cause of cancer-related death in the world. Hence, there was an urgent need to develop novel agents for the treatment of pancreatic cancer. In this paper, nardoguaianone L (G-6) is isolated from N. jatamansi, which inhibited SW1990 cells colony formation and cell migration, and induced cell apoptosis. Furthermore, we analyzed the differential expression proteins after treatment with G-6 in SW1990 cells by using iTRAQ/TMT-based quantitative proteomics technology, and the results showed that G-6 regulated 143 proteins' differential expression by GO annotation, including biological process, cellular component, and molecular function. Meanwhile, KEGG enrichment found that with Human T-cell leukemia virus, one infection was the most highly enhanced pathway. Furthermore, the MET/PTEN/TGF-ß pathway was identified as a significant pathway that had important biological functions, including cell migration and motility by PPI network analysis in SW1990 cells. Taken together, our study found that G-6 is a potential anti-pancreatic cancer agent with regulation of MET/PTEN/TGF-ß pathway.

Tabersonine Inhibits the Lipopolysaccharide-Induced Neuroinflammatory Response in BV2 Microglia Cells via the NF-κB Signaling Pathway.

The occurrence and development of neurodegenerative diseases is related to a variety of physiological and pathological changes. Neuroinflammation is one of the major factors that induces and aggravates neurodegenerative diseases. The most important manifestation of neuroinflammation is the activation of microglia. Therefore, inhibiting the abnormal activation of microglia is an important way to alleviate the occurrence of neuroinflammatory diseases. In this research, the inhibitory effect of tabersonine (Tab) on neuroinflammation was evaluated by establishing the BV2 neuroinflammation model induced by lipopolysaccharide (LPS). It was found that Tab significantly inhibited the production and expression of nitric oxide (NO), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS) in BV-2 cells stimulated by LPS. In addition, Tab can also inhibit the activation of nuclear factor-κB (NF-κB) induced by LPS, thus regulating inflammatory mediators such as inducible nitric oxide synthase (iNOS). These results indicated that Tab regulated the release of inflammatory mediators such as NO, IL-1ß, TNF-α, and IL-6 by inhibiting NF-κB signaling pathway, and exerting its anti-neuroinflammatory effect. This is the first report regarding the inhibition on LPS-induced neuroinflammation in BV2 microglia cells of Tab, which indicated the drug development potential of Tab for the treatment of neurodegenerative diseases.

Fluorometric assay based on the in situ formation of silicon nanoparticles for the determination of ß-glucuronidase.

As a prodrug-converting enzyme, ß-glucuronidase (ß-GCase) is a lysosomal enzyme participating in the release of glucose from glucopyranosyl glycoside. In this work, for the first time, we have developed an analytical method exhibiting fluorometric signals for straightforward determination of ß-GCase using silicon nanoparticles (Si NPs). Via hydrothermal treatment, in the water bath of 70 °C for 50 min, dopamine (DA) reacts with (3-[2-(2-aminoethylamino) ethylamino] propyltrimethoxysilane) (AEEA) to produce green fluorescent Si NPs. Enlightened by such easy reaction and ß-GCase-triggered specific hydrolysis of dopamine-4-ß-D-glucuronide (DA-GCU) into DA, we have designed an analytical method for ß-GCase sensing through the production of Si NPs. Therefore, through the designed sensing platform, ß-GCase activity was monitored, and the limit of detection (LOD) for this study was 0.02 U/L. Furthermore, the feasibility of the method was assessed by measuring ß-GCase activity in human serum where recoveries and RSD were in the ranges 99-104% and 1.37-3.44, respectively.

Association between preadmission low-density lipoprotein cholesterol concentration and risk of large intracerebral hemorrhage: Results from the Kailuan study.

BACKGROUND: To examine the association between low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of a large hematoma volume after intracerebral hemorrhage (ICH). METHODS: Patients from the Kailuan study (Tangshan, China) who were hospitalized with ICH during 2006 and 2020 were included in this study. The concentration of lipid concentrations, hematoma volume and other clinical characteristics were retrospectively collected and analyzed. Hematoma volumes were measured on the first available brain scan using the ABC/2 method. LDL-C concentrations were obtained from the last physical examination before the occurrence of ICH. LDL-C concentration was categorized into four groups in accordance with the quartiles. Logistic regression was used to assess the association between LDL-C concentrations and the risk of a large hematoma volume of ≥30 ml. A generalized linear regression model was used to analyze the dose-response relationship between LDL-C concentration and hematoma volume. RESULTS: A total of 836 patients with ICH were evaluated. In the Multivariate logistic regression, compared to the second quartile of LDL_C, the first quartile of LDL_C had a significantly higher risk of a large hematoma volume (OR 2.49 [95% CI 1.54-4.01]), and the higher quartile of LDL_C is not associated with higher odds of large hematoma volume. In the generalized linear regression model, the adjusted ß for the association between LDL-C concentration and hematoma volume was 9.46 (95% confidence interval 2.87-16.04), whereas higher LDL-C concentration was not associated with a large hematoma volume. CONCLUSIONS: This study confirmed that low LDL-C concentrations prior to ICH are associated with a higher risk of a large hematoma volume.

Chemical constituents from the roots of Zanthoxylum bungeanum Maxim. and their neuroprotective activities.

Twenty-two isolates, including two previously undescribed compounds identified as benzoyltembamide (1) and P-benzoyphenethyl anisate (21), were isolated and identified from a methanol extract of the roots of Zanthoxylum bungeanum Maxim. (Rutaceae) using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data analysis such as HR-ESI-MS, 1D and 2D NMR, IR and UV, as well as single-crystal X-ray diffraction for crystalline compounds. All the compounds (except for compound 16) were isolated from the roots of Z. bungeanum for the first time. Selected compounds were evaluated for their antioxidant activities. Compound 18 attenuated the H2O2-induced cytotoxicity and blocked the accumulation of ROS in SH-SY5Y cells, and exhibited potent neuroprotective activity.